Are You Confident of the Diagnosis?

Behçet's syndrome is a chronic, relapsing, multisystemic, autoimmune vasculitis. The clinical presentation varies depending on which organ systems are involved (mucocutaneous, ocular, cardiovascular, musculoskeletal, gastrointestinal or neurologic). The international criteria for diagnosis require oral aphthous ulcers 3 times in 12 months (Figure 1) plus any two including genital ulcers, uveitis or retinal vasculitis, skin lesions, or positive skin pathergy. Thus, this can fall under the purview of a dermatologist with multiple potential presentations.

Figure 1.

Figure 1. Oral ulceration seen in a patient with Behcet's syndrome.

The mucous membrane lesions are typically confined to oral and genital aphthous ulcers. The skin lesions, however, can be quite heterogeneous and include pustular vasculitis/pseudo-folliculitis, erythema nodosum and acneiform eruptions.

Characteristic findings on physical examination

If a patient meets the criteria for Behçet's syndrome with multisystem involvement, no specific dermatologic investigation may be needed. In the setting of aphthous ulcers, a detailed history and clinical examination may be sufficient. Aphthous ulcers present as painful, well-demarcated ulcers with an erythematous ring and pseudomembranous slough at the base. Lesions have a subtle 1-2 days prodrome, last 7 to 10 days and resolve without scarring.

If biopsies are performed, pathology would be the nonspecific findings of an aphthous ulcer (a mixed, reactive, dermal infiltrate beneath (including neutrophils, macrophages, and lymphocytes) a disrupted epithelium) (Figure 2). In general, a neutrophilic vascular reaction pattern is considered representative of the cutaneous lesions of Behçet's syndrome. A test for pathergy may assist in confirming the diagnosis.

Figure 2.

Figure 2. Neutrophilic infiltrate seen in a biopsy from a pustule in a patient with Behcet's syndrome (H&E).

Biopsies for H&E and direct immunofluorescence can rule out bullous disease and cancer. Other items in the differential can be ruled out using serologic testing (ESR, ANA, TSH, IgA and IgG tissue transglutaminase, RPR and HIV), determination of B12, folate, and PCR (HSV and VZV).

Who is at Risk for Developing this Disease?

The likelihood of a patient with oral aphthous ulcers evolving into a patient meeting the criteria for Behçet's syndrome will vary greatly depending on geography. The highest prevalence of Behçet's syndrome occurs in the populations along the historical Silk Road trading route stretching from the Mediterranean through the Middle East to the Far East. Behçet's syndrome is quite rare in the United States. Males are more frequently involved than females, with ratios varying depending on the population studied. Onset can occur at any age but is most common in the third decade.

Severe disease is associated with being male and young age at onset with higher frequency of major organ involvement and mortality. Smoking cessation in patients with Behçet's syndrome can increase the number and frequency of mucocutaneous lesions, especially oral aphthae.

What is the Cause of the Disease?

Etiology

Pathophysiology

Behçet's syndrome is an autoimmune, inflammatory condition of unknown etiology. The pathophysiology is likely multifactorial. There is a genetic tendency with a strong association to HLA-B51. Dysregulated immune responses to infectious triggers or trauma have been postulated but not proven.

Systemic Implications and Complications

Behçet's syndrome is a multisystem disease; therefore, extracutaneous implications are many and varied. However, ocular involvement, experienced by up to 80% of patients, is the leading cause of morbidity. Referral to ophthalmology and close monitoring are of paramount importance. Early identification and aggressive treatment of ocular disease can prevent blindness.

Treatment Options

There is no cure for Behçet's syndrome so treatment is aimed at symptom control. Because flares and remissions are expected, treatment may not need to be continuous.

APHTHOUS ULCER TREATMENT

Can be approached in the same way as those of recurrent aphthous stomatitis, the main difference being that an ointment is the preferred vehicle for application to the genitals.

Optimal Therapeutic Approach for this Disease

The aggressiveness of treatment should be titrated to the aggressiveness of active disease. Fear of potential disease severity should not lead to aggressive treatment as there is no proven long-term benefit to this approach. Additionally, the risk of morbidity from medication side effects should always be considered. The organ system in which unchecked inflammation has the greatest potential morbidity should dictate treatment. Thus, the dermatologist's role in treatment may be secondary to another specialist (e.g., ophthalmologist, neurologist, or rheumatologist).

In mild mucocutaneous disease, topical corticosteroids and NSAIDs may prove sufficient. If systemic medications are required, colchicine is a simple first-line drug that may benefit multiple disease manifestations and does not require blood work. Most patients can tolerate twice daily dosing of colchicine and many can tolerate three pills daily if dosed as one in the morning and two at bedtime. Pentoxifylline is a less expensive but likely less effective alternative.

Patient Management

Managing a patient with Behçet's syndrome requires a collaborative effort amongst specialists. The clinicians involved are determined by the organ system involvement. Their degree of individual involvement may vary with the course of the disease.

Unusual Clinical Scenarios to Consider in Patient Management

A multisystem inflammatory disease with a relapsing/remitting nature unfortunately dictates an unpredictable clinical course for most patients.

What is the Evidence?

(Comprehensive Cochrane review of 15 trials with over 800 randomised patients were used to compare various therapies including topical and systemic but given high risk of bias a meta-analysis could not be conducted.)